Project Summary The perinatal period is a highly plastic period during which environmental factors can shape the development of the brain. One of the major environmental inputs at this stage is maternal care. Poor maternal care and maternal neglect have been implicated in an array of mental health issues. This is most clearly observed in children that spent early life in orphanages with a low caregiver/infant ratio. However, little is known on how maternal presence regulates brain activity in the infant. Neural activity in early life shapes circuit development and can have life-long consequences on brain function. In our preliminary work, we found that maternal presence/absence from the nest regulates the activity of the prefrontal cortex of rat pups at post-natal day 11. Using wireless local field recording, we will test the role of the serotonergic system in the regulation of pups? brain activity by maternal presence/absence from the nest. In our pilot study, we found preliminary evidence suggesting that: (a) maternal presence increases LFP power in low-frequency bands in P11 rat pups in the PFC; (b) serotonergic signaling through 5-HT2 receptors is necessary for this modulation; and (3) enhancing serotonergic signaling, using a serotonin-selective reuptake inhibitor, in isolated P11 rat pups produces an enhancement in LFP power in low-frequency bands similar to the effect produced by maternal presence. The purpose of this R03 proposal is to increase the sample size of these groups to confirm our preliminary results. This work can reveal the mechanism by which maternal presence regulates brain activity in the pup and sets up a paradigm to study environmental regulation of brain activity in the pup.